Tertiary-aminoalkyl esters and amides of 4-quinolylmercaptoalkanoic acids and their preparation



Patented Sept. 18, 1951 UNITED STATES PATENT OFFICE TERTIARY-AMINOALKYL ESTERS AND AMIDES OF 4-QUINOLYLMERCAPTO- ALKANOIC ACIDS AND THEIR PREP- ARATION Alexander R. Surrey, Albany, N. Y., assignor to Sterling Drug Inc.,, Wilmington, Del., a corporation of Delaware No Drawing. Application October 24, 1947, Serial No. 782,015

20 Claims. (Cl. 260-247.1)

This invention relates to tertiary-aminoalkyl esters and amides of 4-quinolylmercaptoalkanoic acids and their preparation, to salts of said esters .and amides, and to methods of preparing such compounds.

My new compounds have the general formula Q-S-XCO--Z-B ethyl, n-propyl, isopropyl, n-butyl, n-amyl, or

the like. The lower alkylene radical, designated 7 as X, includes such groups as methylene, ethylene, trimethylene, l,l-ethylene, 1,2-prop-ylene,

-.2,2-propylene, 2,2-dimethyl-l,3-propylene, or the like. The tertiary-aminoalkyl radical, designated as B, includes such groups as: 2-diethylaminoethyl; 3-dimethylaminopropyl; 2-(l-piperidyD- ethyl; 4- (4-morpholinyl) butyl; S-diethylamino- 2-penty1 5-dimethylamino-pentyl 2- Z-methyl- 1-pyrrolidyl)ethyl; 2-di-nbutylaminoethyl; 3- (2-methyl-l-piperidyl) propyl; and the like.

It is to be understood that the term a 4-quinolyl radical as used in this specification and in the appended claims is generic, and includes 4- quinolyl radicals wherein the quinoline nucleus may be substituted by one or more of such groups as: halo, including chloro, bromo, iodo, and fluoro; lower alkyl, including methyl, ethyl, propyl, amyl, etc.; hydroxy; lower alkoxy, including methoxy, ethoxy, propoxy, etc.; arylo-xy, such as phenoxy; aralkoxy, such as benzyloxy; trihaloalkyl, such as trifiuoromethyl; nitro; amino; substituted amino, such as acetylamino, ethylamino, dimethylamino, benzylamino, etc.; and other substituents.

The following compounds are representative of the basic esters and amides of my invention:

1. 2- (2-methyl-1 -pyrrolidyl) ethyl 4- (7 -chloro- 4-quinolylmercapto) butanoate.

2. 4-diethylaminobutyl 8-bromo-3-methyl-4- quinolylmercaptoacetate.

3. 3 (4 morpholinybpropyl 2 (6 -eth0xy-3- methyl-i-quinolylmercapto) propanoate.

Clix-CE:

4. 3-dimethylamino-2-propyl. 3,6,7-trimethyl- 4-quinolylmercaptoacetate.

H30 CH3 H: N L

5. N (2 di n butylaminoethyl) 2 (7 phenoxy 4 qumolylmercaptmbutanamide.

SCH(C2H:) C ONHCHflCH2N(C(HI-n)i 6. N (3 (1 piperidyDpropyl) 3 ('7 chloro 3 nitro 4 quinolylmercapto)propanamide.

CRT-43E:

CH1 .CHr-C Cl N I 7. N (2 dlethylammoethyl) (3,7 dlchloro- 4-quinolylmercapto) acetamide.

if? Cl N i 0 Ha J Either 4-haloquinolines or"4=q1iiiiolinethiols may be used as starting materials for the' p-rep aration of my new compounds. Treatment of a 4-haloquinoline with a mercaptoalkanoic acid or treatment of a 4-quinolinethio1 with ahaloalkanoic acid, in either case in the presence of base, results in the formation of a 4-quinolylmercaptoalkanoic acid. When esters of the haloor mercapto-acids are used, the corresponding Quinolylmercaptoalkanoic esters are obtained. Thus,- by treating 4,7-dichloroquinoline with mercapto acetic acid, l-chlorot=quinolylmercaptoacetic acid is obtained; and by treating '7-chloro-4- quinolinethiol with" ethyl" 2-bromopropanoate, ethyl 2- (7-ch1oro-4-quinolylmercapto9 propaneate is formed. i

The intermediate i-haloquinoline's are a generally Well known group of compounds." Representative examples of those that can be used in the synthesis of my basic esters and amides are listed asfollows 3,4-dichloroquinolin 3,4,5 trichloi'oquinoline 3,-"4,7-trichloroquin0line B-bromo-4-chloroquinoline 3bromo-4,7-dichloroquinoline 3-iodo-4-chloroquinoline 3-iodo-4,5-dichloroquinoline 4,5,6-trichloroquinoline 4;5 ,=7 -trichloroquino1ine 4,6,8-trich10roquino1ine 4,7,8-trichloroquinoline 4-chloro-5,7dibromoquinoline 3-methyl-4-chloro-7 -io doquinolii'ie 3-methyl-4-ch1oro-8-iodoquinoline 3-methyl-4,5dichloroquinoline i 3-methyl-4,7-dichloroquinoline 3-methyl-4 chloro -7 -bromoduinolin'e 3-methyl-4 chloro-6-bromoquinoline 3-methy1-4-chloro-6-ethoxyquinoline 3,6-dimethyll-chloroquinoline 3-methyl-4,8-dichloroquino1ine 6-methyl-4-chloro-8-methoxyquinoline 3,8-dimethyl-4-chloroquinoline 4,7-dichloroquinoline 4-chloro-7-bromoquinoline- 4-chloro-7-iodoquinoline 4,7-dichloro-G-methoxyquinoline 4,5-dichloroquinoline 3-nitro-4 chloroquinoline 3 amino--chloroquinoline 4-chloro-7-fiuoroquinoline 4-chloro -7 -trifiuoromethylquinoline 4,7-dich1oro-5-methoxyquinoline 4-chloro-7-phenoxyquinoline 3,4-dibromoquinoline 4-ch1or'o-6 nitroquinoiiiie The above 4-haloquinolines, as well as others, have been described 'in'thlitefature (see Surrey et al., J. Am. Chem. Soc. 68, 113; 1244, and 2570 (1946); Steck et al., ibid. 12911325380, and 1241 (1946) Riegel et al., ibid. 1229; Baker et al., ibid. 1267; Mosher et al., ibid. 69, 303M947); Bachman et al., ibid. 365'; Snyder et a1., ibid. 371; and Clinton 'et a1; ibid. 704?? The intermediate 4-quinolinethio1s' are 'agenerally known group of compounds. A convenient 4 way to prepare this type of thiol is to treat the corresponding 4-haloquinoline with thiourea to yield a quinolylthiouronium halide which on treatment with alkali yields the desired 4-quinoline thiol.

The new basic esters and amides of the above general formula can be prepared by a variety of methods. However the method preferred in practicing my invention comprises treating a lower in'alkyl4-quinolylmercaptoalkanoate with a tertiary-aminoalkanol or a tertiary-aminoalkylamine to yield the corresponding basic ester or amide; respectively. For example, 2-diethyl aminoethyl 2-' ("'7-chloro-4-quinolylmercapto) prois panoa'te is obtained when a mixture of methyl 2-(7-chloro-4-quinoly1) mercaptopropanoate and an excess of Z-diethylaminoethanol in a petroleum ether fraction comprising mixed octanes is refluxed"forabout six to twelve hours or until in) the reaction is complete as judged, for instance, by cessation-of alcohol -formatio'n.- Similarly,

N-'(4 dimethylaminobutyl) (fi-m'ethoxyq quinolylmercapto) acetamide is obtained from' methyl 6 meth0xy-4-quinolylmercaptoacetate and 4-di'- 2: methylaminobutylamine.

The basic-esters'of my invention also can be prepared by heatingla tertiary-aminoalkyl halide with the appropriate 4-quinolylmercaptoalkanoic acid suspended in an aliphatic alcohol such' as :m ethanol, isopropanol, and the like. Thus, treatment of 5-chloro-4-quinolylmercaptoacetic acid with 2-diethylaminoethyl chloride in such a manner yields 2-diethylaminoethyl 5-ch1oro-4-quin- 4 olylmercaptoacetate.

ingta 4-quinolylmercaptoalkanoyl halide with a' tertiary-aminoalkanol or a tertiary-aminoalkylamine, respectively. Thus, Z-diethylaminoethyl 5.", '7-chloro-4-quino1ylmercaptoacetate or N-(2-diethylaminoethyl) '7 -chloro-4-quinolylmercaptoacetamide is obtained by treating 'l-chloro- 4-quinolylmercaptoacetyl chloride with Z-die'thylaminoethanol or 2-diethylaminoethylamine, re-

60 spectively.

The basic-esters and amides of my invention have the same properties, as pharmaceuticals, whether employed asthe free bases, which are the active compounds, orand often more con- 05 venient1yas their salts with non-toxic inorganic or organic acids; so it will be understood that the free bases and their salts are equivalents with respect to the instant invention. Among the acids which may be employed to form'the salts 10" are hydrochloric, phosphoric, sulfuric, sulfamic,

tartaric, citric, benzoic, and the like.

Also comprehended by my invention are the intermediate quinolylmercaptoalkanoic acids, simple derivatives thereof, e.- g.- lower alkyl esters,

' 75* amides, and methods of preparingtthe same In addition, the amides ofmy inventioncan' be prepared by treating a 4-ha1oquinoline with Further, it to be understoodth'at, while the invention is described in the following examples with particular reference to specific 'embodiments, it is not to be limited thereto, but rather is defined by the appended claims.

EXAMPLE 1 A. 7-chloro-4-quinoZinethiol.--To a warm solution of 19.8 g. of 4,7-dichloroquinoline in 200 ml. of absolute alcohol is added 7.6 g. of thiourea. After the resulting solution has been shaken for a few minutes, the entire contents of the flask solidify. The white solid is collected and dissolved in water. The resulting solution is made alkaline with sodium carbonate whereupon a yellow-orange solid separates. This solid is dissolved in dilute sodium hydroxide solution and the solution filtered. The small amount of solid that is removed at this stage is the byproduct, bis('7-chloro-4-quinolyl)sulfide, which melts 166-7 C; after recrystallization from pyridine. The alkaline filtrate i acidified with acetic acid to give the yellow product, 7-chloro- 4-quinolinethiol, which, after recrystallization from acetic acid, melts'at 196-'7 C.

B. 2-(? chloro-4 -quinolylmercapto) propanoic acid.-A mixture of 19.5 g. of l-chloro-l-quinolinethiol, 8 ml. of sodium hydroxide, 200 ml. of ethanol, and 18.1 g. of ethyl 2-bromopropanoate is refluxed with stirring for six hours. The alcohol is removed by distillation, and the resulting ester is hydrolyzed by heating with dilute sodium hydroxide solution. The. acid is precipitated with hydrochloric acid, dissolved in a dilute solution of sodium bicarbonate, and reprecipitated with acetic acid. The purified product, 2-(7-chloro-4 quinolylmercapto)propanoic acid, after recrystallizationfrom ethanol, melts at 202-4 C. The methyl ester hydrochloride, prepared by treating this acid with methanol in the presence of concentrated sulfuric acid, isolating the resulting ester, and treating the ester with methanol saturated with hydrogen chloride, melts at l6'78 C. after recrystallization from isopropanol.

Other compounds prepared by the above procedure include: 3-('7-chloro-4-quinolylmercapto) propanoate (from 3-chloropropanoic acid), M. PL212-4 C., and methyl ester thereof, M. P.

84.586 C.; 7-chloro-4 quinolylmercaptoacetic acid (from chloroacetic acid), M. P. 228-9" C. with decomposition, and methyl ester thereof, M. P. 99.5-l00.5 C.

These 4-quinolylmercaptoalkanoic acids also can-be prepared by reacting the appropriate 4- haloquinoline with a mercaptoalkanoic acid in *the manner described-in the following preparation of '7-chloro-4-quinolylmercaptoacetic acid: A mixture of 19.8 g. of 4,7-dichloroquinoline, 11 g. of mercaptoacetic acid, and ml. of pyridine is refluxed for three hours, and then made alkaline with sodium hydroxide solution. After removal of the pyridine by steam distillation, the residual alkaline solution is acidified with acetic acid. The resulting precipitate is collected, and heated on a steam bath with alcohol to leach out impurities. It is then further purified by dissolution in dilute sodium'bicarbonate solution followed by precipitation with acetic acid, A mixed melting point determination of this product, 7- 'chloro-4-quinolylmercaptoacetic acid, with the acid prepared by the previously described method (from 7chloro4-quinolinethiol and chloroacetic acid) shows no depression. Similarly, the methyl esters prepared from both acids are iden- 5 tical. The ethyl ester melts at 60-1 C. and the amide prepared by treating the methyl ester with alcoholic ammonia at room temperature, melts at 213-4 C.

Other acids, and simple alkyl esters thereof, prepared by this procedure, i. e. from a 4-haloquinoline and a mercaptoalkanoic acid, include those represented by the following formula:

' where Y, Y, and R have the meanings given in the following table:

Table I R= H, R= CH3, Y Y M.P./C. M. ./0.

5-01 H 221-2 102. 5-3. 5 H H 233-4 1 192-3 6-0OH3 H 236-7 225-3 5 7-01 3-CH3 186-8 77-8 H 3-CH3 179-81 62-3 8-OC2H5 3 CH2 198-9 81-2 (i-Br 41H: 197-9 76. 5-7 acre 3 CH3 -2 55-0 7-01 2cm 229-30 102-4 7-01 3-Br 202-4 76-8 5-01 S-OHa 159-90 0-00113 s CH3 192-4 57-8 8 00m 3 CH: 178-230 81. 5-2

1 Melting point of hydrochloride.

The above acids are purified by recrystallization, e. g. from ethanol, or by reprecipitation from an alkaline solution using an acid such as acetic acid. The corresponding esters are readily purified generally by recrystallization from nonpolarsolvents such as petroleum ether, benzene, etc., and in some instances e. g. with methyl 6- bromo-3-methyl-4.-quinolylmercaptoacetate, polar solvents such as methanol can be used.

O. z-diethylaminoethyl 2 7-chZo-ro-4-quino- Zylmercapto propanoute dihydrochloride. A mixture ofone mole of methyl 2-(7-chloro-4- quinolylmercapto)propanoate and four moles of 2-diethylaminoethanol dissolved in a petroleum ether fraction comprising mixed octanes is refluxed in a flask adapted with a water separator for about six to twelve hours or until no more methanol separates. The rate of reflux is maintained at such a rate that practically no peethyl 2- ('l-chloro-4-quino1ylmercapto) propanoate dihydrochloride, after recrystallization from ethanol, melts at 199-201 C. and has the formula,

Other compounds which can be prepared by .the like.

' acid in 60 ml. of dry isopropanol is added 6.8 g. of

'by several recrystallizations from ethanol. product, 2-diethylaminoethy1 -chloro-4-quino- :the above procedureiainclude uthose. represented by"'-the:' following formula:

In addition, other basic esters can be prepared using the intermediate esters shown inTable I as well as other related alkyl quinolylmercaptoalkanoates. Such basic esters include the following: 3-diethylaminopropyl 3-bromo-7-chloro- 3n 4-quinolylmercaptoacetate, 4-dimethylaminobutyl 6-methoxy-3-methyl-4-quinolylmercaptoacetate, 3- (Z-methyl-l-piperidyl) propyl .3-(7-chloro-2-methyl-4-quinolylmercapto)butanoate, and

EXAMPLE 2 2 diethylaminoethyl 5echlofimel-quinlolylmercaptoacetate hydrochloride-To a' hot suspension of 12.7 g. of 5-chloro-4-quinolylmercaptoacetic 2-diethy1aminoethyl chloride. After stirring for about fifteen mintues, a clear solution is obtained; after about twenty minutes the contents of the flask solidify. The solid is collected andpurified lylmercaptoacetate hydrochloride, melts at 199- 201 C. and has the formula LNJ EXAMPLE 3 A. N- (Z-diethylaminoethyl) -chloro-4.-quinolylmercaptoacetamide hydrochloride This preparation iscarried outlike'that described in Example l--C, except that 26.8 g of methyl '7-chlorom .4-quinolylmercaptoacetate and 18 g. of12-diethyl- .aminoethylamine are used. Thea-product, N-2- diethylaminoethyl 'l-chloro -'4-quinolylmercaptoacetamide hydrochloride, after recrystallization from alcohol-acetone-ether; melts at 132-3 85 C. and has .the formula SCH2CONHCHzCH2N(CzHs)7 B. N-(3-diethylaminopropyl) -7-chloro-4-quinoZyZmercaptoacetamide.A mixture of 26.8 g. of

This 4.

l of 3-diethylaminopropylamine, .and 200*mluoi' ."Ihe'above procedures can be used inthe'prepara'tion of. related basic amides having the formula where Y and Y have the meanings given-in Table III:

Table III:

iM P h 11.1. or Y Y 0 droc hclloride,

1 The free bases are recrystallized from petroleum ether or etherpetroleum ether.

The hydrochlorides are recrystallized from an cthanolacetoncether combination or l'rom'cthanol.

In addition, by using the above general procedures (Example 3A and 3B) the basic amides of: my invention are derived from other .alkyl quinolylmercaptoalkanoates such additional basic amides include: N- (2-dimethylaminoethyl) -3- ('7 chloro-4-quino1y1mercapto) propanamide, N- (5-diethy1amino-2-pentyl) -2- (3-bromo-7 -ch1or0- 4-quinolylmercapto) butanamide, and the like. Also, di-N-substituted amides are formed when the above procedures'are followed-but using an -N-alkyl-tertiary-aminoalkylamine; for example -N-( -dimethylaminopropyl) -N'-ethyl ("l-chloro- 4:-quinolylmercapto)acetamide is prepared from methyl 17-chloro-4-quinolylmercaptoacetate .and 5N-ethyl-N;N:dimethyl-1,3-propylenediamine.

EXAMPLE 4 "A. N (2 -.dz'ethylaminoethyl) mercaptoacetamide.-'A=solution of 0.30-mo1e of ethyl mercarito- --acetateand 0.60. mole. of 2-diethylaminoethy1- amine in '200 m1. of dry benzene is refluxed =or eight hours in a flask adapted with a waterseparator to remove ethanol formedby the reaction. Removal of the solvent by distillation in vacuo leavesa residueof-43.6 g. of crude N--(2.-.diethyl- 1.aminoethyl).mercaptoacetamide which. is suitable for user-in the next step-ofssynthesis (see-Ex- -ample; 4-3) .-B..-'N 1! 2 --d7'ethylam'inoethyl)- 7 chloro 4- .-quinolylmercaptoacetamide.To a solution of 22 methyl 7-chloro-4-quin0lylmercaptoacetate;20 g. 75 .g.s0f 1 crude .-.N.-'(2rdiethylaminoethyl) mercaptoethanol containing i g. of sodium hydroxide is added 20 'g. of 4,7-dichloroquinoline, and the resulting mixture is refluxed with stirring for four hours. The solid which separates is filtered, and the filtrate is concentrated in vacuo to give about 13 g. of crude product, which is dissolved in dilute hydrochloric acid and reprecipitated with sodium hydroxide solution. The solid thus obtained is recrystallized from ether to yield the purified product, N-(Z-diethylaminoethyl)-7- chloro-4-quinolylmercaptoacetamide, M. P. 98.5- 9.5 C, (a mixed melting point with 'a sample of the base of the hydrochloride prepared according to the procedure described in Example 3 gives no depression).

The procedure described in Examples 4A and amides of my invention. Thus, these procedures can be carried out using other lower alkyl mercap- H toalkanoates, other tertiary-aminoalkylamines, and other 4-haloquinolines; for example, methyl 3-mercaptopropanoate and B-dimethylaminopropylamine can be reacted according to the procedure of Example 4A to give N-(3-dimethylaminopropyl) -3-mercaptopropanamide, and then this reacted with 6-methoxy-4-chloroquinoline, as in Example 4B, to yield N-(3-dimethylaminopropyl) 3 (6 methoxy 4 quinolylmercapto)propanamide as the final product.

' Application of this mode of preparation to the synthesis of the corresponding basic esters of our invention is not as satisfactory as for the amides since the tertiary-aminoalkyl mercaptoalkanoates, which are formed by substituting a tertiary-aminoalkanol for 2-diethylaminoethylamine in Example 4A, are partially hydrolyzed under the alkaline reaction conditions of Examp le 4B. In contrast, the amides formed by the procedure described in Example 4A, are rather resistant to hydrolysis under the conditions employed in Example 4--B.

EXAMPLE Methyl 7-chloro-4-quinolyZmercaptoacetate.-- A mixture of 5 g. of 7 -ch1oro-4-quinolylmercaptoacetic acid, 3.4 g. of phosphorous pentachloride, and 100 ml. of dry benzene is refluxed with stirring for about one hour. The benzene is distilled in vacuo; 100 ml. of methanol is added'to the residue; and the resulting mixture is refluxed for one hour. After removal of the methanol by distilling in vacuo, the residue is dissolved in water and the resulting solution is made alkaline with aqueous sodium carbonate solution. The

solid that separates is collected by filtration and recrystallized from petroleum ether to yield 2.5 g. of methyl 7-chloro-4-quinolylmercaptoacetate. M. P. 98-1G0 0., having the formula If the above procedure is carried out using in place of methanol either 2-diethylaminoethanol or Z-diethylaminoethylamine there is obtained as the final products 2-diethylaminoethyl 'l-chloro- 4-quinolylmercaptoacetate and N-(2-diethylaminoethyl) '7 chloro 4 quinolylmercaptoacetamide, respectively.

I claim:

1. A compound having the formula where Q is a 4-quinolyl radical, X is a lower alkylene radical, Z is a member of the; group consisting of O, NH, andN-(lower ,alkyl), and B is a lower tertiary-aminoalkyl group, the tertiary-amino portion of which is selected from the group consisting of lower dialkylamino, l-piperidyl, lower alkyl-l-piperidyl, l-pyrrolidyl, lower alkyl-l-pyrrolidyl and 4-morpholinyl, and acidaddition salts thereof.

2. A compound having the formula I v Q--SX-C0.0-.-B I where Q is a 4 quinolyl radical, 'X is a lower alkylene radical, and B is a lower dialkylaminoalkyl group, and acid-addition salts thereof.

3. A compound having the formula where Q is a 4-quinolyl radical, X is a lower alkylene radical, and B is a lower dialkylaminoalkyl group, and acid-addition salts-thereof.

4. A compound having the formula Y I Q-SCH:z-COOB where Q is a l-quinolyl radicaland B is a lower dialkylaminoalkyl group, and acid-addition salts thereof.

5. A compound having the formula Q-S-CH2--CONH -B where Q is a 4-quinolyl radical and B is a lower dialkylaminoalkyl group, andacid-addition salts thereof.

6. The process of preparing a compound having the formula comprises reacting a compound of the formula,

QSX-COOR, where R is a lower alkyl group, with a compound of the formula, B-Z-H.

'7. The process of preparing a compound having the formula Where Q is a 4-quinolyl radical, X is a lower alkylene radical, and B is a lower dialkylaminoalkyl group, which comprises reacting a compound of the formula, QSXCOOR, where R is a lower alkyl group, with a compound of the formula, BOH.

8. The process of preparing a compound having the formula where Q is a 4-quinolyl radical, X is a lower alkylene radical, and B is a lower dialkylaminoalkyl group, which comprises reacting a compound of the formula, QSX+COOR, where R is a lower alkyl group, with a compound of the formula BNHz.

9. The process of preparing a compound having the formula where Q is a 4-quinolyl radical and B is a lower dialkylaminoalkyl group, which comprises reacting a compound of the formula,

'where'R'is a-lower alkyl group',with a compound ofi-the formula BOH;

10. The process of-preparing a-compound having the formula where .Q'is a'zi-quinolyl'radical andiBis a lower dialkylaminoalkyl group, which comprises reacting a compound of the formula,

where R is a loweralkyl group, with a compound having: the .formula':BNH2.:

11. A compound 'having the-formula SCH1'G oo-B Cl N where-Bis a lower dialkylaminoalkyl group, and acid-addition salts thereof 12. Z-diethylaminoethyl 'l-chlorol-quinolylmercaptoacetate, and acid-addition salts thereof.

13. 2-'dimethylaminoethyl' '7-chloro-4-quinolylmercaptoacetate, and acid addition'salts thereof.

14. 2-(1-piperidyl) ethyl 7-chloro-4-quinolylmercaptoacetate; and acid-addition salts thereof. 15. 2-(4-morpholinyl) ethyl l-chlnrol-ouinm lylmercaptoacetate, and acid addition salts thereof.

16. The process of preparing acompound having the formula S-CHz-COO-B where-"1B "v is a lower dialkylaminoalkyl group, which'comprises reacting a "lower 'alky1'7- chloro- 12 4-quinoly1mercaptoacetate with a basic alcoholoi the formula LBOH.

17.. The processof preparing Z-diethylaminoethyl 7-chloro-4-quinolylmercaptoacetate, which comprises reacting a: lower alkyl 'T-chloro-4- REFERENCES CITED The following references are of record in the file of this patent:

UNITED STATES PATENTS Number Name Date 1,825,623 I Miescher .Sept. 29, 1931 1,841,970 Miescher Jan.'19,' 1932 OTHER REFERENCES Wiseloglez. Survey of Antimalarial Drugs,

1941-1945" (J. W. Edwards; Ann Arbor, Mich.; 1946) vol..II, part 2,1page 1058.

Steckz. J. Am..Chem...Soc., vol. 68, page 129 (Jan..1946)'.

Schonhofer: Zeit...physiol. Chem, vol. 274, pp. 1-8 (1942). I 

15. 2-(4-MORPHOLINYL) ETHYL 7-CHLORO-4-QUINOLYLMERCAPTOACETATE, AND ACID - ADDITION SALTS THEREOF. 